In the manufacture of pharmaceutical products, it is common to utilize an apparatus known as a “roller compactor” to compress a powder composition into a ribbon or into pellets for further processing or utilization. In a roller compactor, the powder composition is fed into a nip between the peripheries of two opposed, counterrotating, rollers.
Feeding can be effected by any of a variety of feeding devices. Typical feeding devices include a screw feeder, which can have a single rotating screw, or a plurality of intermeshing screws, belt conveyors, which can have one or more endless belts, and various other forms of conveying devices suitable for transporting a powder.
The peripheries of the rollers can be simple cylindrical surfaces, or they can have mold cavities in which the powder is compacted and formed into a desired shape. In the case of rollers having simple cylindrical surfaces, the product of the roller compactor is typically in the form of a ribbon of compacted powder, which can be broken up, if desired, by a cutting device. On the other hand, if the rollers have mold cavities in their peripheries, they can deliver discrete pellets of compacted powder.
Roller compaction has been successful for producing various pharmaceutical products. However, product quality problems have been encountered. It is possible to overcome these problems by making adjusting various parameters of the operation of the compactor, but doing so is difficult and requires a great deal of operator experience. In addition, some materials that are highly temperature sensitive, and materials that are processed at temperatures near their melting point are particularly susceptible to problems when subjected to roller compaction.
In tablet coating, which is typically carried out by spraying a coating onto a bed of tablets being tumbled in a rotating drum-like device known as a “coating pan” coating conditions such as the spraying rate, and the rate of evaporation of the coating vehicle, affect tablet temperature. Accordingly measurement of tablet temperature is useful in monitoring the coating operation and in controlling various coating parameters. Heretofore, temperature measurement in coating pans has been carried out using various forms of thermometers such as non-contact infrared temperature measurement devices and other forms of temperature probes. It has also recently been proposed to incorporate into a bed of tablets one or more mobile temperature measurement devices, each having the size, shape, and weight of one of the tablets being coated, and containing a temperature measuring device coupled to a miniature telemetry transmitter for sending temperature data to a remote receiver as a modulated radio signal.
The known temperature measurement devices used for monitoring coating processes do not provide sufficient information for good control of the coating operation, or for designing large coaters by “scaling up” on the basis of temperature measurements taken using a smaller experimental coater. In particular, known temperature measurement devices used in coaters provide little information concerning the coater spray pattern, and are therefore of limited use in determining the relationship between the rate of flow of coating material through the spray nozzles and the amount of coating deposited on the tablets.
In fluid bed drying, where warm air is caused to flow upward through a bed of particulate material in a drying vessel, the temperature of the material tends to stratify, so that the temperatures in the lower parts of the dryer are higher than the temperatures in the upper parts. At the start of a drying operation, the temperature differences between different levels are large. However, as drying proceeds, the temperatures in the upper parts of the dryer increase, and the temperature differences between the upper and lower parts tend to decrease. Thus, early in a drying operation, the temperature difference is high. However, when new material is introduced into the fluid bed dryer, whether in a continuous feed mode or in a batch mode, the temperatures in the upper zones of material become higher. The result is either that excessive drying occurs in the upper zones of the dryer, or the time required for drying decreases. The latter is of course the more desirable result.
The temperature differentials in a fluid bed dryer can be observed using conventional thermal probes. However, conventional probes do not provide adequate information concerning the progressive changes in temperature differentials that occur over time to enable an operator to control drying parameters such as air temperature, material flow, and drying time.
In high shear wet granulation, a powder is subjected to the action of a moving blade in the presence of a binder applied to the material by spraying through one or more spray nozzles. The cooling that occurs due to evaporation of the binder affects the granulation process, but does not take place uniformly within the granulator. Cooling is also affected by the spray pattern of the nozzles. Conventional temperature probes cannot adequately monitor the temperature variations in the material, which can occur both at the surface of the bed as a function of the spray pattern as in a coating operation, and within the bed, as in fluid bed drying.
In spray drying, a slurry of material is sprayed through a nozzle into an atmosphere of heated air, which passes through an exhaust outlet. Conventional temperature measurement techniques used in spray drying measure the temperature of the air at the exhaust outlet, and provide only an indirect, and somewhat unreliable, indication of the actual temperature of the sprayed material as it is being dried. These conventional techniques also lack the ability to monitor the spray characteristics and the temperature profiles within the spray pattern.
In lyophilization, quantities of a wet material are typically placed in a relatively large number of small vials, which are arranged on one or more racks in a chamber in which temperature and pressure can be controlled. The material is first frozen. Then, the pressure and temperature in the chamber are adjusted to a level at which the water in the frozen material sublimes. Thereafter, residual moisture is removed by applying a vacuum while maintaining the material at a controlled temperature.
In a lyophilization chamber, the duration of each of the above steps is typically determined by measurement of the temperature in selected vials. However, the materials in the vials tend to dry at different rates depending on their location within the chamber, and also depending on the materials themselves, which are not necessarily identical. Therefore, temperature measurement in selected representative vials does not always lead to optimal results.
In the preparation of low dosage pharmaceutical products using liquid dispensing technology, an array of pharmacologically inert carrier tablets or similar substrates is transported past an array of dispensing nozzles that project very small, but accurately controlled doses of an active pharmaceutical substance onto the carriers individually. The droplets are typically in the form of liquids containing the active substance either in solution or in suspension. The droplets form coatings on the carriers, which adhere to the carriers. The carriers are typically subjected to heating to evaporate the liquid component of the coatings. Liquid dispensing technology or “LDT” is described in United States Patent Publication 2006/0017916, published Jan. 26, 2006, the entire disclosure of which is herein incorporated by reference.
In liquid dispensing technology, as in the other processes mentioned above, the temperatures of different carriers in the array of carriers moving past the dispensing nozzles can vary from one carrier to another, and if the heating of the carriers for evaporation of the liquid component of the coatings is not properly controlled, some carriers and the active material adhering thereto could be overheated or others could be insufficiently heated to evaporate the solvent or suspension medium.
Other manufacturing processes in which temperature measurement is utilized include crystallization, precipitation, fermentation and the like, in all of which both spatial and temporal temperature variations occur, often in unpredictable patterns.